Abstract A13: Development of a drug response assessment platform for biopsy-derived tumor models

Our labs have previously described a pharmacogenomic approach to identify therapeutic strategies in cancer cells derived directly from the biopsies of patients. These findings were made in pure cancer cell populations derived on the order of months. Our ultimate goal is to utilize one9s own cancer cells for a personalized in vitro diagnostic test. Therefore, we aimed to develop a reliable method to analyze a high-throughput pharmacological screen in mixed cell populations with minimal cancer cells since this is the reality of fresh samples within weeks of the biopsy. The necessity for this is two-fold: first, the culture of patient biopsies is more successful on an irradiated fibroblast feeder layer and, second, noncancerous patient cells, including stromal fibroblasts, often survive biopsy culture. We identified a cocktail of two monoclonal antibodies, one against cytokeratin 8 and another against cytokeratin 18, as a consistent identifier of lung cancer cells that could be used in a high-throughput immunofluorescence-based assay. Drug sensitivity experiments with the immunofluorescence-based assay on patient-derived lung cancer cells mixed with feeder or stromal fibroblasts produced dose-response curves consistent with a pure cancer cell viability assay. We plan to utilize this assay to test the accuracy of patient-derived tumor models, obtained within weeks of biopsy, in mimicking patients9 responses to targeted therapy. Ultimately, we hope this approach could help determine therapeutic choices for individual patients. Citation Format: David P. Kodack, Matthew Held, Leah Damon, Dana Lee, Melissa Parks, Richard Dicecca, Max Greenberg, Jeffrey A. Engelman, Cyril H. Benes. Development of a drug response assessment platform for biopsy-derived tumor models. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A13.